SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
13
01
2022
accepted:
03
05
2022
pubmed:
8
7
2022
medline:
9
8
2022
entrez:
7
7
2022
Statut:
ppublish
Résumé
Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.
Identifiants
pubmed: 35798890
doi: 10.1038/s41564-022-01143-7
pii: 10.1038/s41564-022-01143-7
pmc: PMC9352574
doi:
Substances chimiques
Antibodies, Viral
0
Membrane Glycoproteins
0
Spike Glycoprotein, Coronavirus
0
Viral Envelope Proteins
0
spike protein, SARS-CoV-2
0
BNT162 Vaccine
N38TVC63NU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1161-1179Subventions
Organisme : Medical Research Council
ID : MR/V038613/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_20058
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19026
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204721/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00002/11
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT109965MA
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 211153/Z/18/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/W02067X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R019843/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MCUU1201412
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12014/12
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/W005611/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19027
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107653/Z/15/A
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 220977/Z/20/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R024758/1
Pays : United Kingdom
Organisme : Department of Health
ID : NIHR300791
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R004250/1
Pays : United Kingdom
Investigateurs
Susanna Dunachie
(S)
Paul Klenerman
(P)
Eleanor Barnes
(E)
Anthony Brown
(A)
Sandra Adele
(S)
Barbara Kronsteiner
(B)
Sam M Murray
(SM)
Priyanka Abraham
(P)
Alexandra Deeks
(A)
M Azim Ansari
(MA)
Thushan de Silva
(T)
Lance Turtle
(L)
Shona Moore
(S)
James Austin
(J)
Alex Richter
(A)
Christopher Duncan
(C)
Rebecca Payne
(R)
Amy Ash
(A)
Cherian Koshy
(C)
Beatrix Kele
(B)
Teresa Cutino-Moguel
(T)
Derek J Fairley
(DJ)
James P McKenna
(JP)
Tanya Curran
(T)
Helen Adams
(H)
Christophe Fraser
(C)
David Bonsall
(D)
Helen Fryer
(H)
Katrina Lythgoe
(K)
Laura Thomson
(L)
Tanya Golubchik
(T)
Abigail Murray
(A)
Dawn Singleton
(D)
Shaun M Beckwith
(SM)
Anna Mantzouratou
(A)
Magdalena Barrow
(M)
Sarah L Buchan
(SL)
Nicola Reynolds
(N)
Ben Warne
(B)
Joshua Maksimovic
(J)
Karla Spellman
(K)
Kathryn McCluggage
(K)
Michaela John
(M)
Robert Beer
(R)
Safiah Afifi
(S)
Sian Morgan
(S)
Andrew Mack
(A)
Angela Marchbank
(A)
Anna Price
(A)
Arthur Morriss
(A)
Catherine Bresner
(C)
Christine Kitchen
(C)
Ian Merrick
(I)
Joel Southgate
(J)
Martyn Guest
(M)
Owen Jones
(O)
Robert Munn
(R)
Thomas R Connor
(TR)
Thomas Whalley
(T)
Trudy Workman
(T)
William Fuller
(W)
Amita Patel
(A)
Bindi Patel
(B)
Gaia Nebbia
(G)
Jonathan Edgeworth
(J)
Luke B Snell
(LB)
Rahul Batra
(R)
Themoula Charalampous
(T)
Angela H Beckett
(AH)
Ekaterina Shelest
(E)
Samuel C Robson
(SC)
Anthony P Underwood
(AP)
Ben E W Taylor
(BEW)
Corin A Yeats
(CA)
David M Aanensen
(DM)
Khalil Abudahab
(K)
Mirko Menegazzo
(M)
Amelia Joseph
(A)
Gemma Clark
(G)
Hannah C Howson-Wells
(HC)
Louise Berry
(L)
Manjinder Khakh
(M)
Michelle M Lister
(MM)
Tim Boswell
(T)
Vicki M Fleming
(VM)
Christopher W Holmes
(CW)
Claire L McMurray
(CL)
Jessica Shaw
(J)
Julian W Tang
(JW)
Karlie Fallon
(K)
Mina Odedra
(M)
Nicholas J Willford
(NJ)
Paul W Bird
(PW)
Thomas Helmer
(T)
Lesley-Anne Williams
(LA)
Nicola Sheriff
(N)
Sharon Campbell
(S)
Veena Raviprakash
(V)
Victoria Blakey
(V)
Christopher Moore
(C)
Fei Sang
(F)
Johnny Debebe
(J)
Matthew Carlile
(M)
Matthew W Loose
(MW)
Nadine Holmes
(N)
Victoria Wright
(V)
M Estee Torok
(ME)
William L Hamilton
(WL)
Alessandro M Carabelli
(AM)
Andrew Jermy
(A)
Beth Blane
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Carol M Churcher
(CM)
Catherine Ludden
(C)
Dinesh Aggarwal
(D)
Elaine Westwick
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Ellena Brooks
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Georgina M McManus
(GM)
Katerina Galai
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Ken Smith
(K)
Kim S Smith
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MacGregor Cox
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Mireille Fragakis
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Patrick Maxwell
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